BUILDING ZINC FINGERS BY SELECTION - TOWARD A THERAPEUTIC APPLICATION

被引：172

作者：

WU, H ^{[1
]}

YANG, WP ^{[1
]}

BARBAS, CF ^{[1
]}

机构：

[1] SCRIPPS RES INST, DEPT MOLEC BIOL, LA JOLLA, CA 92037 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 1995年 / 92卷 / 02期

关键词：

GENE THERAPY; TRANSCRIPTIONAL REGULATION; PHAGE DISPLAY; COMBINATORIAL LIBRARIES; HUMAN IMMUNODEFICIENCY VIRUS;

D O I：

10.1073/pnas.92.2.344

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

A phage display approach was utilized to modify the specificity of each of the three fingers of the murine transcription factor Zif268. Selections were performed by using the consensus binding sequence of the natural protein and a conserved sequence in the genome of the type 1 human immunodeficiency virus. By using an extensive randomization strategy, the entire 3-bp specificity of a finger has been changed. Rapid analysis of selected zinc fingers was facilitated by the development of an immunoscreening assay for DNA binding and specificity. To investigate the mechanism of binding and specificity, the binding kinetics of Zif268 and 10 selected variants were determined in real time with an assay based on surface plasmon resonance. Differential mechanisms for sequence-specific recognition were observed. No evidence in support of a single general coding relationship between zinc finger and target DNA sequence was observed. The prospects for the development of this class of proteins in human therapy are considered.

引用

页码：344 / 348

页数：5

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